{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T21:30:04Z","timestamp":1792877404380,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"43","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020"},{"name":"Marie Sk\u0142odowska-Curie","award":["766118"],"award-info":[{"award-number":["766118"]}]},{"DOI":"10.13039\/501100009379","name":"IZKF of W\u00fcrzburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009379","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Glycoprotein VI (GPVI) is a platelet collagen\/fibrin(ogen) receptor and an emerging pharmacological target for the treatment of thrombotic and thrombo-inflammatory diseases, notably ischaemic stroke. A first anti-human GPVI (hGPVI) antibody Fab-fragment (ACT017\/glenzocimab, KD: 4.1 nM) recently passed a clinical phase 1b\/2a study in patients with acute ischaemic stroke and was found to be well tolerated, safe, and potentially beneficial. In this study, a novel humanized anti-GPVI antibody Fab-fragment (EMA601; KD: 0.195 nM) was developed that inhibits hGPVI function with very high potency in vitro and in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Fab-fragments of the mouse anti-hGPVI IgG Emf6.1 were tested for functional GPVI inhibition in human platelets and in hGPVI expressing (hGP6tg\/tg) mouse platelets. The in vivo effect of Emf6.1Fab was assessed in a tail bleeding assay, an arterial thrombosis model and the transient middle cerebral artery occlusion (tMCAO) model of ischaemic stroke. Using complementary-determining region grafting, a humanized version of Emf6.1Fab (EMA601) was generated. Emf6.1Fab\/EMA601 interaction with hGPVI was mapped in array format and kinetics and quantified by bio-layer interferometry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Emf6.1Fab (KD: 0.427 nM) blocked GPVI function in human and hGP6tg\/tg mouse platelets in multiple assays in vitro at concentrations \u22655 \u00b5g\/mL. Emf6.1Fab (4 mg\/kg)-treated hGP6tg\/tg mice showed potent hGPVI inhibition ex vivo and were profoundly protected from arterial thrombosis as well as from cerebral infarct growth after tMCAO, whereas tail-bleeding times remained unaffected. Emf6.1Fab binds to a so far undescribed membrane proximal epitope in GPVI. The humanized variant EMA601 displayed further increased affinity for hGPVI (KD: 0.195 nM) and fully inhibited the receptor at 0.5 \u00b5g\/mL, corresponding to a &amp;gt;50-fold potency compared with ACT017.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>EMA601 is a conceptually novel and promising anti-platelet agent to efficiently prevent or treat arterial thrombosis and thrombo-inflammatory pathologies in humans at risk.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehae482","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T17:21:15Z","timestamp":1723828875000},"page":"4582-4597","source":"Crossref","is-referenced-by-count":41,"title":["The humanized platelet glycoprotein VI Fab inhibitor EMA601 protects from arterial thrombosis and ischaemic stroke in mice"],"prefix":"10.1093","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1112-8400","authenticated-orcid":false,"given":"Stefano","family":"Navarro","sequence":"first","affiliation":[{"name":"Institute of Experimental Biomedicine I , Josef-Schneider-Stra\u00dfe 2, 97080 W\u00fcrzburg ,","place":["Germany"]},{"name":"Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, University of Wuerzburg , Josef-Schneider-Str. 2, 97080 W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Talucci","sequence":"additional","affiliation":[{"name":"Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, University of Wuerzburg , Josef-Schneider-Str. 2, 97080 W\u00fcrzburg ,","place":["Germany"]},{"name":"Department of Neurology, University Hospital W\u00fcrzburg , Josef-Schneider-Str. 11, 97080 W\u00fcrzburg 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Center for Integrative and Translational Bioimaging, University of Wuerzburg , Josef-Schneider-Str. 2, 97080 W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Orth","sequence":"additional","affiliation":[{"name":"EMFRET Analytics GmbH , Eibelstadt ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2474-5165","authenticated-orcid":false,"given":"Guido","family":"Stoll","sequence":"additional","affiliation":[{"name":"Institute of Experimental Biomedicine I , Josef-Schneider-Stra\u00dfe 2, 97080 W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans M","family":"Maric","sequence":"additional","affiliation":[{"name":"Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, University of Wuerzburg , Josef-Schneider-Str. 2, 97080 W\u00fcrzburg 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